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In strategy, competence, quality and flexibility Recent developments in Pharmacovigilance from the Regulator’s Perspective
In strategy, competence, quality and flexibility
Recent developments in Pharmacovigilance
from the Regulator’s Perspective
• Pharmacovigilance• Pharmacovigilance
• Regulatory Affairs Operations
• Medical Writing & toxicology
The introduction of new PV legislation in July 2012 is the biggest change to the
regulation of human medicines in the European Union (EU) since 1995.
Recent developments in Pharmacovigilance
Similarly, the United States Food and Drug Administration (USFDA) has become
more open to inclusion of non-safety data collection in its safety surveillance more open to inclusion of non-safety data collection in its safety surveillance
mandates and more proactive risk management approach.
Recent developments in Pharmacovigilance
Trends-
1. To strengthen the instruments of protection of human health-
• Continuous monitoring of the risk-benefit ratio of drugs
• Greater transparency
• Power to penalize producers for the failure to meet
Pharmacovigilance obligations
2. Partial harmonization of the different Pharmacovigilance systems
New definition of adverse drug reaction:
• An adverse drug reaction is a response to a medicinal product which is
noxious and unintended.
• Also covers
� Medicinal errors
� The use outside the terms of the marketing authorization,
Recent developments in Pharmacovigilance
� The use outside the terms of the marketing authorization,
o Overdose
o off-label use
o Misuse
o Abuse
o occupational exposure
Volume 9 a?
Recent developments in Pharmacovigilance
The key to the success of the legislation is the Good Pharmacovigilance
Practice (GVP) document which replaced Volume 9A.
Main Pillars
1. The new Good Vigilance Practice Guidelines (GVP)
2. The Pharmacovigilance Risk Assessment Committee (PRAC)
3. The Pharmacovigilance System Master File (PSMF)
4. Using a Periodic Benefit Risk Evaluation Report (PBRER)
5. More stringent ICSR submission rules
6. Publishing summaries of Risk Management Plans (RMP) 6. Publishing summaries of Risk Management Plans (RMP)
7. Requirement to perform Post-Approval Safety Studies (PASS)
8. Assignment of an Additional Monitoring Status
9. Commitment to openness and transparency
10. EudraVigilance policy to disclose postmarketing safety information to the Public
Risk Management
RMP
• In accordance to new legislation, RMP should be risk
proportionate and needs to be submitted for all new
products.
• Educational materials for HCPs and patients are required in • Educational materials for HCPs and patients are required in
RMP for a new product.
• The authorized products require RMP if there are issues
affecting the risk benefit balance.
• Summaries of RMPs shall be made public publicly available
via web portals.
PRAC
• PRAC is a new scientific committee within
the EMA, created to ensure access to the
best scientific and medicinal expertise for
the evaluation of the safety of medicines and
Risk Management
the evaluation of the safety of medicines and
risk minimization measures, with the
ultimate goal of reducing ADRs.
• Will have regulatory oversight of RMPs
PRAC: Role
Risk Management
Risk Detection/ Signal
Detection
Risk Assessment
Risk Minimization
PV PlanningCommunication
of risk & benefit/risk
Risk Evaluation and Mitigation Strategies (REMS)
• The USFDA has obligation for manufacturers to implement special risk
management programs, called REMS.
• If the benefits of drug outweigh the risks, then the applicant having an
Risk Management
approved application for new drug or abbreviated new drug or
biological medicinal product has to submit REMS. The proposed REMS
must be submitted within 120 days of the USFDA notification for the
protection of public health.
PV system Master File (PSMF)
As per the new legislation, Detailed Description of Pharmacovigilance
System (DDPS) will no longer be required and is replaced by PSMF. MA
applicants and MAHs are required to maintain PSMF.
On request, the PSMF should be provided within seven days to CAs. The
annexes of the PSMF contain comprehensive data demonstrating the
current state of the PV system, including
• An overview of all marketing authorisations covered by the PSMF
together with information on presence on the market (also outside EU)
and specific safety monitoring requirements
PV system Master File (PSMF)
• Results of the current performance assessment [e.g. timeliness of
Individual Case Safety Reports (ICSRs) reporting and PSUR submission,
safety variations and adherence to RMP requirements]
• An audit schedule and critical findings from previous PV audits
• A detailed overview on the company’s written procedures
Periodic Reporting
• In EU, PSUR is replaced with Periodic Benefit Risk Evaluation Report
(PBRER).
• The PBRER does not work anymore as a detailed listing of ICSRs.
• The submission of periodic reports is also exempted for MAHs of generic,
well-established used, homeopathic or traditional-use herbal medicinal
products. products.
• Six monthly reports, summary bridging reports, or addendum reports will
not be accepted.
• New assessment procedure involving PRAC
• Assessment reports of PSURs will be published on EMA web portal.
xEVMPD
• The Medicinal Product Dictionary has actually been in existence since
2005
• All MA Holders have been able to submit basic details of their products
to the EMA
• Was not mandatory, so consequently the EVMPD contains less than • Was not mandatory, so consequently the EVMPD contains less than
25% of the estimated 528,000 products authorized for use in the EU,
and the data that is there is likely to be out of date.
• The original legislation was amended in December 2010
…..the EMA shall set up a list of all medicinal products for human use
authorized in the EU, and that marketing authorization holders were required,
by 2 July 2012 at the latest, to electronically submit to the EMA information on
all medicinal products for human use authorized or registered in the EU using
xEVMPD
all medicinal products for human use authorized or registered in the EU using
the format defined by the EMA, and keep it up to date thereafter….
Phased approach
• Initial submission phase: July 2011 - January 2014
• Transition maintenance phase: February 2014 – 2016
xEVMPD
• Transition maintenance phase: February 2014 – 2016
� February 2014 - June 2014 (preparatory phase)
� June 2014 onwards (Transition phase)
xEVMPD
Partial harmonization of the different Pharmacovigilance
systems
Simplify the sponsors’ activities and
increase the efficacy of pharmacovigilance
The ICH of Technical Requirements for Registration of The ICH of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) has elaborated a
pharmacovigilance guideline for medicines approved in the
U.S., the E.U. and Japan
Pharmacovigilance relevant sections of Module 1 of CTD
MedDRA
